Significant new advances were made in developing novel therapeutic strategies to cure chronic retroviral infections. Previous studies in our lab showed that regulatory T cells suppressed anti-viral CD8+ T cell responses in mice chronically infected with Friend retrovirus. Based on this knowledge we used a combination of adoptive lymphocyte transfer and immunomodulatory antibodies designed to render CD8+ T cells resistant to suppression by regulatory T cells. The strategy produced short term reductions in virus loads of greater than 99%. Current studies are focused on improving the longevity of virus load reductions. In addition, our current studies are also optimizing the therapeutic dosing and scheduling protocols and eliminating the requirement for adoptive lymphocyte transfers to achieve virus reductions. We are also actively engaged in determing precisely how the therapeutics affect various aspects of the immune system in terms of understanding both the mechanisms of action and possible safety issues. Progress has also been made in determing how regulatory T cells are induced during infection and how the induction of these cells is affected by vaccination. Important discoveries on the tissue distribution of virus-induced regualtory T cells have also been made that have ramifications for further development of therapeutics. Recent reports indicate that regulatory T cell suppression of CD8+ T cell responses is also occurring in HIV infections in humans and the degree of suppression correlates with viral loads. Thus our mouse model is extremely relvant to human retroviral infections and may lead to new therapies to treat chronic HIV infections.